U.S. Pat. No. 5,552,270 to Khrapko et al. describes a device for sequencing DNA by hybridization. The device comprises an oligonucleotide array rigidly bound to a solid substrate. The oligonucleotide array consists of a multiplicity of gel portions separated from one another. Each gel portion contains one oligonucleotide of desired length.
Test DNA fragments are labeled with either a radioactive marker or a fluorescent marker. A solution including a buffer and the labeled test DNA fragments is applied to the device. The solution fully covers the gel portions containing immobilized oligonucleotides. The labeled test DNA fragements hybridize with one or more of the oligonucleotides. After performing a washing step, hybridization events are detected by detecting the radioactive marker or the fluorescent marked. A sequence associated with the test DNA fragments is reconstructed by analyzing detection data.
It is desirable to detect the hybridization events without requiring that the test DNA fragments be labeled with radioactive markers or fluorescent markers.